According to the American Cancer Society, breast cancer is the most prevalent malignancy among women in the United States, with more than 200,000 new cases diagnosed per year (Jemal et al., Cancer J. Clin. 56: 106-130 (2006)). Significant advances have been made in mammography and other imaging modalities over the last few decades. As a result, more patients are diagnosed in the early-stage of the disease, for which breast conservation therapy (BCT) has become the treatment of choice.
Compared with mastectomy, BCT provides a comparable outcome with superior cosmetic results and reduced psychological and emotional trauma (Fisher et al., N. Engl. J. Med. 347(16): 1233-1241 (2002); Veronesi et al., N. Engl. J. Med. 347(16): 1227-1232 (2002); Liljegren et al., J. Clin. Oncol. 17(8): 2326-2333 (2000); Clark et al., J. Natl. Cancer Inst. 88(22): 1659-1664 (1996); and Gray et al., Intl. J. Radiat. Oncol. Biol. Phys. 21: 347-354 (1991)). BCT, however, is a complex, protracted treatment. Patients diagnosed with early-stage breast cancer first undergo a surgical procedure called lumpectomy, in which the tumor and its surrounding tissue, referred to as a margin, are removed. Ideally, a margin of sufficient size is removed so that no tumorous tissue is left behind. However, breast cancer is naturally multi-focal, and, consequently, there are normally small tumor foci scattered around the gross tumor (Holland et al., Cancer 56: 979-990 (1985)). Furthermore, mammograms and magnetic resonance images are obtained under different geometric conditions as compared to surgery, lumpectomy is performed without any direct image guidance, and the geometric uncertainty of surgery is no better than about a centimeter. Therefore, realistically, even though the probability of finding a tumor focus decreases sharply with an increase in distance from the gross tumor (Holli et al., Br. J. Cancer 84(2): 164-169 (2001); Liljegren et al. (2000), supra; and Clark et al. (1996), supra), one or more micro-sized tumor foci are left behind. This is why patients subsequently undergo radiation therapy to treat the surgical margin. If post-operative radiation is not received, about 35% of lumpectomies are expected to fail locally (Early Breast Cancer Trial's Collaborative Group, New Engl. J. Med. 333: 1444-1455 (1995)).
Currently, standard radiation therapy involves irradiation of the whole breast over the course of about 5-7 weeks. Brachytherapy also has been used to treat the surgical margin (Baglan et al., Intl. J. Radiat. Oncol. Biol. Phys. 50(4): 1003-1011 (2001); King et al., Am. J. Surg. 180(4): 299-304 (2000); and Wazer et al., Intl. J. Radiat. Oncol. Biol. Phys. 53(4): 889-897 (2002)), and involves the interstitial introduction of radioactive seeds of high or low activities into the breast. Accelerated partial breast irradiation (APBI), which involves irradiation of the surgical bed of the breast over the course of about 1-2 weeks, is currently being tested in several clinical trials (Vicini et al., J. Clin. Oncol. 19(7): 1993-2001 (2001)).
Unfortunately, external radiation beams, whether employed over 1-2 weeks or 5-7 weeks, can lead to pulmonary (Lingos et al., Intl. J. Radiat. Oncol. Biol. Phys. 21: 355-360 (1991); and Rothwell et al., Radiother. Oncol. 4: 9-14 (1985)) and cardiovascular (Corn et al., J. Clin. Oncol. 8: 741-750 (1990); Dodwell et al., Australasian Radiol. 38: 154-156 (1994); and Rutqvist et al., Intl. J. Radiat. Oncol. Biol. Phys. 22: 887-896 (1992)) damage, skin and soft tissue fibrosis (Johansen et al., British J. Radiol. 67: 1238-1242 (1994)), arm edema (Wallgren, Acta Oncologica 31(2): 237-242 (1992)), and increased risk of secondary cancer (Inskip et al., J. Natl. Cancer Inst. 86(13): 983-988 (1994); and Wallgren (1992), supra). These drawbacks adversely affect the quality of life of patients undergoing BCT.
The improved sensitivity and specificity of three-dimensional MRI (3-D MRI) has challenged surgeons to provide a less invasive, equally effective, and cosmetically superior alternative to a lumpectomy. Consequently, efforts to develop minimally invasive techniques for breast cancer surgery have increased (Dowlatshahi et al., The Amer. J. of Surgery 182: 419-425 (2001)). These efforts include hot (Jeffrey et al., Arch. Surg. 134: 1064-1068 (1999); and Izzo et al., Proc. Am. Soc. Clin. Oncol. 19: 80A (2000)) and cold (Staren et al., Arch. Surg. 132: 28-33 (1997)) percutaneous ablation, and the use of automated needles (Liberman et al., Am. J. Roentgenol. 173: 1315-1322 (1999); and Burak et al., Arch. Surg. 135: 700-703 (2000)), cannulae (D'Angelo et al., Am. J. Surg. 174: 297-302 (1997); Chesbrough et al., Radiology 209: 197 (1999); and Liebman et al., Am. J. Roentgenol. 172: 1409-1412 (1999)), and lasers (Harries et al., Br. J. Surg. 81: 1617-1619 (1994); Mumtaz et al., Radiology 200: 651-658 (1996); Milne et al., Lasers Surg. Med. 26: 67-75 (2000); and Dowlatshahi et al., Breast J. 2: 304-311 (1996)).
One of the more widely tested hot ablative techniques is radiofrequency ablation (RFA) (Jeffrey et al. (1999), supra; and Izzo et al. (2000), supra). Under general anesthesia, the RFA probe is inserted into the tumor under sonographic guidance. The radiofrequency current applied to the electrode causes the temperature near the electrode to rise gradually to a target temperature, e.g., 95° C., over a period of about 5 to 7 minutes. The temperature is then maintained at the target temperature for about 15 minutes, after which it is allowed to cool down for about 1 minute. A cold ablative technique, i.e., cryotherapy, involves circulating liquid nitrogen to the tip of a probe to form an ice ball to destroy cells. Although these ablative methods are meant to be minimally invasive, they have to be performed under general anesthesia. In addition, it is difficult, if not impossible, to conform precisely the damage generated to the shape of the tumor, such that unnecessary damage to surrounding normal tissue is avoided or minimized. These techniques have not been demonstrated to be able to replace surgery.
Due to the precision of image-guided needle biopsy, surgeons have tried to use a vacuum-assisted biopsy technique to remove gross and microscopic tumors piecemeal (Liberman et al. (1999), supra; and Burak et al. (2000), supra), or to use a large-core cannula in conjunction with stereotactic localization to remove a non-fragmented, single, large-core specimen (D'Angelo et al. (1997), supra; Chesbrough et al. (1999), supra; and Liebman et al. (1999), supra). Reported results indicate that complete excision with such techniques appears to correlate better with tumors smaller than about 0.7 cm. Even with small tumors, however, residual tumors are left behind in about 70% of the patients. Therefore, these percutaneous image-guided techniques, though less invasive, cannot replace surgery.
Radiosurgery enables ablation of a tumor with sub-milliliter precision. It has proven to be effective for all sites where a single, high dose can be safely delivered. Most stereotactic radiosurgery has been performed on intracranial tumors using a dedicated device, like the Gamma Knife or a linear accelerator, with multiple arced beams focused at the tumor site. Radiosurgery also has been successfully used for extracranial sites, such as the lung and the spine. Radiosurgery is especially effective for metastatic cancer, e.g., metastatic breast cancer, in the brain. A single dose of about 16-24 Gy to the metastatic tumor eradicates the tumor in more than 85% of the cases (Vesagas et al., J. Neurosurg. 97(5 Suppl.): 507-510 (2002); and Kondziolka et al., Cancer 104(12): 2784-2791 (2005)), although doses of less than 20 Gy are generally delivered with a palliative intent.
To date, the inventors are not aware of anyone who has applied stereotactic radiosurgery to the breast. In this regard, the inventors are not aware of any device that can deliver a high dose of radiation to a cancerous region of the breast safely and accurately with surgical precision. Unlike radiosurgery of intracranial tumors, where the radiation beam can approach the intracranial lesion from more than a 2π solid angle, the breast can only be approached from limited, unobstructed angles by external radiation beams, such as those generated by a linear accelerator. Furthermore, unlike the skull, which can be securely fixated into a coordinate system so that there is no geometric difference between imaging and treatment, such immobilization has never been achieved with a breast.
In view of the above, it is an object of the present invention to provide a method of using stereotactic radiosurgery to treat a cancerous region in a breast. It is a further object of the present invention to provide equipment for use in the method. These and other objects and advantages, as well as additional inventive features, will become apparent from the detailed description provided herein.